October 25, 2011 (San Francisco, California) — Laboratory studies conducted at the Memorial Sloan-Kettering Cancer Center in New York City suggest that triple-negative breast cancer (TNBC) might respond to treatment with an oncolytic agent.

The findings were reported here at the American College of Surgeons 97th Annual Clinical Congress.

"We found that [the mutant herpes virus] NV1066 is an effective oncolytic agent against triple- negative breast cancer in vitro and in vivo," said Sepideh Gholami, MD, a research fellow in the laboratory of Yuman Fong, MD, which is considered to be at the forefront in oncolytic viral therapy research.

"Oncolytic viruses are attractive therapeutic agents that destroy tumor cells without the accompanying destruction of normal cells," she said. The mitogen-activated protein kinase (MAPK)signaling pathway is known to be important in TNBC, and activated (phosphorylated) MAPK signaling has been shown to mediate efficient replication of NV1066 through the deletion of the delta gamma(1)34.5 gene.

In other words, she said, TNBC cells have high levels of phosphorylated MAPK, a protein that promotes tumor growth and contributes to resistance to current therapies. The herpes virus specifically targets cells that overexpress this protein, which is the rationale for this approach. The study aimed to determine whether NV1066 could kill TNBC cells effectively. The researchers also examined the functional effects of NV1066 on the MAPK signal transduction pathway during viral infection.

Dr. Gholami and colleagues infected 5 different TNBC cell lines with the NV1066 herpes simplex virus. After treatment with the virus, the most sensitive cell lines demonstrated a 90% cell kill rate within 1 week; the less sensitive lines demonstrated a 70% cell kill rate.

"TNBC cells support efficient viral replication, with over 1 million copy numbers observed, which is more than a 1000-fold increase," she said.

"Since baseline phosphorylated MAPK levels positively correlated with sensitivity to NV1066, they might therefore be used as a clinical marker for selecting patients for viral therapy," she suggested.

Tumor Regression Almost CompleteThe researchers created flank tumors and injected them with NV1066 or a control compound. Within 5 days, tumor volume significantly decreased in the experimental group; within 3 weeks, they observed "near-complete tumor regression," Dr. Gholami reported.

Monday, October 24, 2011

FRIDAY,
Oct. 21 (HealthDay News) -- The breast cancer drug letrozole, marketed
as Femara, may be more effective than tamoxifen at preventing the
return of breast cancer and improving survival among older women with
hormone-sensitive breast cancers, a new study reports.

In the study, published online Oct. 21 in The Lancet Oncology,
the researchers updated data from an ongoing study of about 8,000
women, which compares the two drugs alone as well as the use of both
Femara and tamoxifen sequentially.

Femara outperformed
tamoxifen in terms of breast cancer recurrence and survival, the study
found. Moreover, giving Femara alone to women was more effective than
giving it sequentially following tamoxifen. The new study was partially
funded by Novartis, the drug company that makes Femara.

The
hormone estrogen feeds hormone-sensitive cancers, and blocking it may
help stave off a recurrence. Femara is part of a class of breast cancer
drugs known as aromatase inhibitors. These drugs block the body's
production of estrogen via the enzyme aromatase. Tamoxifen is a
selective estrogen receptor modulator, which means that it acts like
estrogen in certain tissues, but not in others, namely the breast.
Aromatase inhibitors are given alone or in combination with tamoxifen.

After an average eight years of follow-up, the team of researchers
from the United States, Europe and Australia found that women who took
Femara for five years after breast cancer treatment had a "20 percent
reduced risk of their breast cancer coming back and were 21 percent less
likely to die, compared with women given tamoxifen alone," one of the
lead authors of the study, Meredith Regan of the Dana-Farber Cancer
Institute in Boston, explained in a journal news release.

Neither
sequential treatment of tamoxifen followed by Femara, or in the
reverse order, significantly decreased the likelihood of relapse or
death compared to Femara alone, the team reported.

"Femara
alone is the best way to go," said Dr. Stephanie Bernik, chief of
surgical oncology at Lenox Hill Hospital in New York City. "The hope
was that the combination would improve survival, but this was not the
case," said Bernik, who was not involved with the study.

Breast
cancer survivors who are being treated with tamoxifen should discuss
their options with their doctor. "Talk to your doctor about switching
to an aromatase inhibitor," Bernik said. "Tamoxifen is still an
excellent drug, but the aromatase inhibitors are better. If the plan
was to switch drugs, you may want to talk to [your] doctor about going
straight to the aromatase inhibitor," she added.

Dr. Hannah
Linden, a medical oncologist at the Seattle Cancer Care Alliance, said
that many women don't want to take these drugs because of a fear of
side effects or the desire to put breast cancer behind them. "The
study stresses the importance of taking these medications," she said.
This is not to say they don't have their share of side effects; they
do, she noted.

Serious side effects seen with Femara include bone fractures and increases in cholesterol
levels. Some research has suggested that aromatase inhibitors may also
increase the risk for heart disease. Tamoxifen side effects may
include blood clots, strokes, uterine cancer and cataracts.

Dr. Maura N. Dickler, a breast cancer medical oncologist at the
Memorial Sloan-Kettering Cancer Center in New York City, said that
aromatase inhibitors have been her go-to drugs for women with
estrogen-positive breast cancers for a while.

Some women report
joint pain and other nuisance side effects from aromatase inhibitors
and have to go back to tamoxifen, Dickler said. "In these cases,
getting in an aromatase inhibitor for some time is beneficial," she
noted. "We can individualize treatment based on the side effects and
the tolerability for each woman."

Cost may be an issue for some
women, but the gap in price between the two drugs is narrowing, Dickler
added. Femara is now available as a generic, which helps reduce its
costs, but tamoxifen is still probably less expensive, she said.

Overall,
"this is an exciting update with longer follow-up," Dickler said of
the study. Since last results were reported in 2005, there was a 32
percent increase in the number of women who had a relapse. "These women
can do well for a long time and still relapse many years later," she
said. "It just reminds us that women relapse during year five through
10 as much as zero through five. Breast cancer is an indolent disease
and you can remain disease free for a long time, but relapse can still
happen."

Tuesday, October 11, 2011

Vitamin-breast cancer link eyed in studies

October 10, 2011 by DELTHIA RICKS / delthia.ricks@newsday.com

Certain supplements may prove detrimental to women who've survived breast cancer, while older women may be at a slightly elevated risk from regular use of vitamin and mineral pills, medical investigators have found in two separate investigations.

In a study of 2,300 women, researchers at Columbia University in Manhattan found women treated for early stage breast cancer and who took vitamin A, lutein or beta-carotene, supplements known collectively as carotenoids, faced a greater risk of dying from recurrent cancer -- and virtually all other causes of death.

By contrast, those treated for early-stage breast cancer who routinely took vitamins C or E had a lower recurrence risk after five years than those who didn't take the vitamins. Vitamins C and E are known as antioxidants that protect cells.

"My main take home message here is that we're seeing antioxidant supplements working in one direction and the carotenoids working in another," said Dr. Heather Greenlee, who led the examination.
A second study in the Archives of Internal Medicine involving 38,000 women reported by researchers in Finland found U.S. women 75 and older who consumed any dietary supplements, including multivitamins, folic acid, iron and copper, had a 2.4 percent increased risk of death than those avoiding the pills. There was no risk associated with calcium and vitamin D.

Greenlee said it's unclear why vitamins C and E appeared to have a beneficial effect on cancer survivors -- if they did at all. It is possible, Greenlee said, that it wasn't vitamins C and E thwarting a recurrence, but other healthy behaviors the women shared that helped them avoid a second bout with cancer.

She said her research tried to help physicians guide breast cancer patients about vitamin use.
"We are not referring to vitamin A consumed in foods," Greenlee added. "Here, we are referring to supplements."

She noted that neither the American Cancer Society nor the American Institute of Cancer Research recommend vitamin supplements as a way to avoid cancer. A growing body of scientific evidence suggests supplements can be dangerous, Greenlee said.

Leah Pasquarella, chief clinical dietitian at Southside Hospital in Bay Shore, said the United States has evolved into a pill-popping culture where people think vitamins are beneficial without questioning how they affect the body. "I think we rely on them too much as a substitute for healthy foods and that's a problem," Pasquarella said.

Supplements, she added, are not regulated by the Food and Drug Administration, and potencies differ from one manufacturer to the next.

In Greenlee's research, findings were based on questionaires answered by women who had been diagnosed with early-stage breast cancer. More than 80 percent said they took at least one supplement containing antioxidants, either as a multivitamins or as single pill within two years of diagnosis.
Women who said they took a single supplement of either vitamin C or vitamin E six to seven days a week had a lower risk of cancer recurrence. Greenlee's analysis is reported in the current issue of the journal Cancer.

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